There is an ever increasing number of therapeutic intravenous (IV) fluids being developed for delivery that are susceptible to gases such as oxygen and carbon dioxide, and thus need to be packaged properly to avoid degradation. These therapeutic fluids must be preserved and protected from contact by such gases to maintain the efficacy of the therapeutic fluid.
For example, hemoglobin solutions are known to lose their ability to function as oxygen therapeutic agents during storage. A hemoglobin solution loses its ability to function as a oxygen therapeutic agent because of spontaneous transformation of oxyhemoglobin in the solution to methemoglobin, a physiologically inactive form of hemoglobin that does not function as a oxygen therapeutic agent by releasing oxygen into a patient's bloodstream. To improve shelf life, oxygen therapeutic agents can be refrigerated, frozen or deoxygenated in efforts to control the oxygenation state of the hemoglobin within the solution.
A common storage container for a hemoglobin solution is a flexible container made of plastic polymer film, most notably an intravenous (IV) bag. Further, the container for a hemoglobin solution should be made from a material that complies with U.S. Pharmacopeia (USP) Class VI classification (physical, chemical and biocompatibility) and that is non-pyrogenic. Unlike IV bags for many other solutions, IV bags used specifically for hemoglobin solutions stored in a deoxygenated state must also provide a sufficient barrier to the passage of moisture vapor and other gases to preserve the deoxygenated state of the hemoglobin solution contained therein. Specifically, it is typically desirable for such containers to possess high oxygen barrier properties to enable deoxygenated hemoglobin solutions to be stored for weeks or months at room temperature. For example, ethylene vinyl alcohol (EVOH) is known to provide a high barrier to the ingress of oxygen.
Containers used for storing hemoglobin solutions are often fabricated from single-ply or multilayer materials. Multilayer foils can be produced via coextrusion and/or lamination. In principle, multilayer-packaging foils and packaging materials for sensitive goods are composed of a thin gas-barrier core layer, which may have been bonded by way of an adhesion-promoter layer or a lamination-adhesive layer to outer layers. For example, a multilayer package of ethylene vinyl acetate/ethylene vinyl alcohol (EVA/EVOH) has previously been used as a primary packaging bag to minimize gas permeability and avoid the formation of inactive methemoglobin. For secondary protection of blood products, it has also previously been known that a metal foil laminate overwrap can be used to protect against potential air leakage and to maintain the product in a deoxygenated state. However, there is a potential drawback of pin holes occurring in these overwrap packages that compromises its air tightness and makes the product unstable. In particular, in the past, clear silicon containing laminates with high oxygen and moisture barrier properties have not been useful in automated packaging equipment because the stress on the material causes it to crack or otherwise lose the desired barrier properties.
Accordingly, there is a need in the field for a packaging system for storing a nonoxygenated hemoglobin solution that possesses superior oxygen barrier properties to prevent the oxidation of hemoglobin and thereby maintain the nonoxygenated hemoglobin solution in a nonoxygenated state until administration.